This study aimed to describe a syndrome that the authors call diffuse lamellar keratitis that follows laser in situ keratomileusis (LASIK) and related lamellar corneal surgery. Noncomparative case series and record review. Thirteen eyes of 12 patients in whom infiltrates developed in the interface after lamellar refractive surgery were studied. Topical antibiotics or corticosteroids or both were administered. Corneal infiltrate appearance, focality, location, and clinical course were measured. Patients presented between 2 and 6 days after surgery with pain, photophobia, redness, or tearing. Ten cases directly followed either myopic keratomileusis or LASIK. Three cases followed enhancement surgery without the use of a microkeratome. All 13 cases had infiltrates that were diffuse, multifocal, and confined to the flap interface with no posterior or anterior extension. The overlying epithelium was intact in each case. Cultures were negative in the two cases cultured. Ten eyes were treated with antibacterial agents; two eyes had fluorometholone four times daily added to the routine postoperative antibacterial regimen, and one eye had the antibacterial agent discontinued and was treated with topical fluorometholone alone. All infiltrates resolved without sequelae. A distinct syndrome of unknown cause of noninfectious diffuse infiltrates in the lamellar interface is described. It can be distinguished from infectious infiltrates by clinical presentation and close follow-up. Patients with the syndrome should be spared the more invasive treatment of infectious keratitis.